Differential PKA activation and AKAP association determines cell fate in cancer cells

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• 作者：Erik D Hedrick (1)
  Ekta Agarwal (1)
  Premila D Leiphrakpam (1)
  Katie L Haferbier (1)
  Michael G Brattain (1)
  Sanjib Chowdhury (1)
  
• 关键词：Colorectal cancer ; IGF1R ; AKAP149 ; Praja2 ; PKA ; XIAP
• 刊名：Journal of Molecular Signaling
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：8
• 期：1
• 全文大小：499 KB
• 参考文献：1. Rodon J, DeSantos V, Ferry RJ Jr, Kurzrock R: Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway: lessons from the first clinical trials. / Mol Cancer Ther 2008,7(9):2575-588. CrossRef
  2. Ryan PD, Goss PE: The emerging role of the insulin-like growth factor pathway as a therapeutic target in cancer. / Oncologist 2008,13(1):16-4. CrossRef
  3. Valentinis B, Baserga R: IGF-I receptor signalling in transformation and differentiation. / Mol Pathol 2001,54(3):133-37. CrossRef
  4. Buck E, Gokhale PC, Koujak S, Brown E, Eyzaguirre A, Tao N, Rosenfeld-Franklin M, Lerner L, Chiu MI, Wild R, / et al.: Compensatory insulin receptor (IR) activation on inhibition of insulin-like growth factor-1 receptor (IGF-1R): rationale for cotargeting IGF1R and IR in cancer. / Mol Cancer Ther 2010,9(10):2652-664. CrossRef
  5. Godsland IF: Insulin resistance and hyperinsulinaemia in the development and progression of cancer. / Clin Sci (Lond) 2009,118(5):315-32. CrossRef
  6. Weber MM, Fottner C, Liu SB, Jung MC, Engelhardt D, Baretton GB: Overexpression of the insulin-like growth factor I receptor in human colon carcinomas. / Cancer 2002,95(10):2086-095. CrossRef
  7. Mulvihill MJ, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, O’Connor M, Pirritt C, Sun Y, Yao Y, / et al.: Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. / Future Med Chem 2009,1(6):1153-171. CrossRef
  8. Pitts TM, Tan AC, Kulikowski GN, Tentler JJ, Brown AM, Flanigan SA, Leong S, Coldren CD, Hirsch FR, Varella-Garcia M, / et al.: Development of an integrated genomic classifier for a novel agent in colorectal cancer: approach to individualized therapy in early development. / Clin Cancer Res 2010,16(12):3193-204. CrossRef
  9. Chowdhury S, Howell GM, Rajput A, Teggart CA, Brattain LE, Weber HR, Chowdhury A, Brattain MG: Identification of a novel TGFbeta/PKA signaling transduceome in mediating control of cell survival and metastasis in colon cancer. / PLoS One 2011,6(5):e19335. journal.pone.0019335" target="_blank" title="It opens in new window">CrossRef
  10. Dubrez-Daloz L, Dupoux A, Cartier J: IAPs: more than just inhibitors of apoptosis proteins. / Cell Cycle 2008,7(8):1036-046. CrossRef
  11. Dohi T, Xia F, Altieri DC: Compartmentalized phosphorylation of IAP by protein kinase A regulates cytoprotection. / Mol Cell 2007,27(1):17-8. j.molcel.2007.06.004" target="_blank" title="It opens in new window">CrossRef
  12. Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC: IAP regulation of metastasis. / Cancer Cell 2010,17(1):53-4. j.ccr.2009.11.021" target="_blank" title="It opens in new window">CrossRef
  13. Chowdhury S, Howell GM, Teggart CA, Chowdhury A, Person JJ, Bowers DM, Brattain MG: Histone deacetylase inhibitor belinostat represses survivin expression through reactivation of transforming growth factor beta (TGFbeta) receptor II leading to cancer cell death. / J Biol Chem 2011,286(35):30937-0948. jbc.M110.212035" target="_blank" title="It opens in new window">CrossRef
  14. Agarwal E, Brattain MG, Chowdhury S: Cell survival and metastasis regulation by Akt signaling in colorectal cancer. / Cell Signal 2013,25(8):1711-719. j.cellsig.2013.03.025" target="_blank" title="It opens in new window">CrossRef
  15. Pidoux G, Tasken K: Specificity and spatial dynamics of protein kinase A signaling organized by A-kinase-anchoring proteins. / J Mol Endocrinol 2010,44(5):271-84. CrossRef
  16. Welch EJ, Jones BW, Scott JD: Networking with AKAPs: context-dependent regulation of anchored enzymes. / Mol Interv 2010,10(2):86-7. CrossRef
  17. Lignitto L, Carlucci A, Sepe M, Stefan E, Cuomo O, Nistico R, Scorziello A, Savoia C, Garbi C, Annunziato L, / et al.: Control of PKA stability and signalling by the RING ligase praja2. / Nat Cell Biol 2011,13(4):412-22. CrossRef
  18. Zhang L, Duan CJ, Binkley C, Li G, Uhler MD, Logsdon CD, Simeone DM: A transforming growth factor beta-induced Smad3/Smad4 complex directly activates protein kinase A. / Mol Cell Biol 2004,24(5):2169-180. CrossRef
  19. Wang J, Yang L, Yang J, Kuropatwinski K, Wang W, Liu XQ, Hauser J, Brattain MG: Transforming growth factor beta induces apoptosis through repressing the phosphoinositide 3-kinase/AKT/survivin pathway in colon cancer cells. / Cancer Res 2008,68(9):3152-160. CrossRef
  20. Donovan EA, Kummar S: Role of insulin-like growth factor-1R system in colorectal carcinogenesis. / Crit Rev Oncol Hematol 2008,66(2):91-8. j.critrevonc.2007.09.003" target="_blank" title="It opens in new window">CrossRef
  21. Schimmer AD, Dalili S: Targeting the IAP family of caspase inhibitors as an emerging therapeutic strategy. / Hematology Am Soc Hematol Educ Program 2005, 215-19.
  22. Schimmer AD, Dalili S, Batey RA, Riedl SJ: Targeting XIAP for the treatment of malignancy. / Cell Death Differ 2006,13(2):179-88. j.cdd.4401826" target="_blank" title="It opens in new window">CrossRef
  23. Awwad RA, Sergina N, Yang H, Ziober B, Willson JK, Zborowska E, Humphrey LE, Fan R, Ko TC, Brattain MG, / et al.: The role of transforming growth factor alpha in determining growth factor independence. / Cancer Res 2003,63(15):4731-738.
  24. Boyd DD, Levine AE, Brattain DE, McKnight MK, Brattain MG: Comparison of growth requirements of two human intratumoral colon carcinoma cell lines in monolayer and soft agarose. / Cancer Res 1988,48(9):2469-474.
  25. Hu YP, Patil SB, Panasiewicz M, Li W, Hauser J, Humphrey LE, Brattain MG: Heterogeneity of receptor function in colon carcinoma cells determined by cross-talk between type I insulin-like growth factor receptor and epidermal growth factor receptor. / Cancer Res 2008,68(19):8004-013. CrossRef
  26. Jiang D, Yang H, Willson JK, Liang J, Humphrey LE, Zborowska E, Wang D, Foster J, Fan R, Brattain MG: Autocrine transforming growth factor alpha provides a growth advantage to malignant cells by facilitating re-entry into the cell cycle from suboptimal growth states. / J Biol Chem 1998,273(47):31471-1479. jbc.273.47.31471" target="_blank" title="It opens in new window">CrossRef
  27. Wang D, Li W, Jiang W, Humphrey LE, Howell GM, Brattain MG: Autocrine TGFalpha expression in the regulation of initiation of human colon carcinoma growth. / J Cell Physiol 1998,177(3):387-95. CrossRef
  28. Andersen MH, Svane IM, Becker JC, Straten PT: The universal character of the tumor-associated antigen survivin. / Clin Cancer Res 2007,13(20):5991-994. CrossRef
  29. Eckelman BP, Salvesen GS, Scott FL: Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. / EMBO Rep 2006,7(10):988-94. j.embor.7400795" target="_blank" title="It opens in new window">CrossRef
  30. Fabregat I: Dysregulation of apoptosis in hepatocellular carcinoma cells. / World J Gastroenterol 2009,15(5):513-20. jg.15.513" target="_blank" title="It opens in new window">CrossRef
  31. Almeida MQ, Stratakis CA: How does cAMP/protein kinase A signaling lead to tumors in the adrenal cortex and other tissues? / Mol Cell Endocrinol 2011,336(1-):162-68. j.mce.2010.11.018" target="_blank" title="It opens in new window">CrossRef
  32. Brattain MG, Levine AE, Chakrabarty S, Yeoman LC, Willson JK, Long B: Heterogeneity of human colon carcinoma. / Cancer Metastasis Rev 1984,3(3):177-91. CrossRef
  33. Brattain MG, Marks ME, McCombs J, Finely W, Brattain DE: Characterization of human colon carcinoma cell lines isolated from a single primary tumour. / Br J Cancer 1983,47(3):373-81. jc.1983.56" target="_blank" title="It opens in new window">CrossRef
  34. Chowdhury S, Ongchin M, Sharratt E, Dominguez I, Wang J, Brattain MG, Rajput A: Intra-Tumoral Heterogeneity in Metastatic Potential and Survival Signaling between Iso-Clonal HCT116 and HCT116b Human Colon Carcinoma Cell Lines. / PLoS One 2013,8(4):e60299. journal.pone.0060299" target="_blank" title="It opens in new window">CrossRef
  35. Chowdhury S, Ongchin M, Wan G, Sharratt E, Brattain MG, Rajput A: Restoration of PTEN activity decreases metastases in an orthotopic model of colon cancer. / J Surg Res 2013,184(2):755-60. j.jss.2013.03.035" target="_blank" title="It opens in new window">CrossRef
  36. Chowdhury S, Sharratt E, Spernyak J, Brattain MG, Rajput A: Anti-tumor activity of IGF1R kinase inhibitor PQIP in colon cancer. / Clin Exp Pharmacol 2013, S4:005.
  37. Jost PJ, Grabow S, Gray D, McKenzie MD, Nachbur U, Huang DC, Bouillet P, Thomas HE, Borner C, Silke J, / et al.: XIAP discriminates between type I and type II FAS-induced apoptosis. / Nature 2009,460(7258):1035-039. CrossRef
  
• 作者单位：Erik D Hedrick (1)
  Ekta Agarwal (1)
  Premila D Leiphrakpam (1)
  Katie L Haferbier (1)
  Michael G Brattain (1)
  Sanjib Chowdhury (1)
  
  1. Eppley Cancer Center, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, 68198-5950, USA
  
• ISSN：1750-2187

文摘

Background The dependence of malignant properties of colorectal cancer (CRC) cells on IGF1R signaling has been demonstrated and several IGF1R antagonists are currently in clinical trials. Recently, we identified a novel pathway in which cAMP independent PKA activation by TGFβ signaling resulted in the destabilization of survivin/XIAP complex leading to increased cell death. In this study, we evaluated the effect of IGF1R inhibition or activation on PKA activation and its downstream cell survival signaling mechanisms. Methods Small molecule IGF1R kinase inhibitor OSI-906 was used to test the effect of IGF1R inhibition on PKA activation, AKAP association and its downstream cell survival signaling. In a complementary approach, ligand mediated activation of IGF1R was performed and AKAP/PKA signaling was analyzed for their downstream survival effects. Results We demonstrate that the inhibition of IGF1R in the IGF1R-dependent CRC subset generates cell death through a novel mechanism involving TGFβ stimulated cAMP independent PKA activity that leads to disruption of cell survival by survivin/XIAP mediated inhibition of caspase activity. Importantly, ligand mediated activation of the IGF1R in CRC cells results in the generation of cAMP dependent PKA activity that functions in cell survival by inhibiting caspase activity. Therefore, this subset of CRC demonstrates 2 opposing pathways organized by 2 different AKAPs in the cytoplasm that both utilize activation of PKA in a manner that leads to different outcomes with respect to life and death. The cAMP independent PKA activation pathway is dependent upon mitochondrial AKAP149 for its apoptotic functions. In contrast, Praja2 (Pja2), an AKAP-like E3 ligase protein was identified as a key element in controlling cAMP dependent PKA activity and pro-survival signaling. Genetic manipulation of AKAP149 and Praja2 using siRNA KD had opposing effects on PKA activity and survivin/XIAP regulation. Conclusions We had identified 2 cytoplasmic pathways dependent upon the same enzymatic activity with opposite effects on cell fate in terms of life and death. Understanding the specific mechanistic functions of IGF1R with respect to determining the PKA survival functions would have potential for impact upon the development of new therapeutic strategies by exploiting the IGF1R/cAMP-PKA survival signaling in cancer.